The first goal is to define the weak interactions between purified receptors and their nuclear acceptor sites. We have recently modified an estradiol ligand affinity chromatography procedure for a single step apparent purification of approximately 3000 fold. This receptor preparation will be subjected to further purification and characterization. The latter includes size and isoelectric point determination, oligodeoxynucleotide binding affinities, molecular substructure and sensitivity to inhibitors of DNA bindings. The receptor will be used as a reagent to detect high affinity binding sites in DNA, alone or in cooperation with chromosomal proteins. The estrogen induced rat uterine proteins will be purified, characterized as to size and isoelectric point and assessed for specific protease activities. Further studies will be performed to relate their protease activity, if this is confirmed, to the developmental process of uterotrophy. Other specific proteases will be examined, again with a specific effect on uterine cytodifferentiation. The goal of both projects will add to our knowledge of steroid hormone modulated processes in normal, and perhaps abnormal growth.